The PROLUNG training network

PROLUNG - a training network of PROVENet

The overarching objective of this training network is to offer transnational and inter-sectoral training for young and talented researchers in the field of ventilation in ICU patients. Our training vision is to develop a cohort of young scientists with the necessary depth and breadth of experience combined with the research and transferable skills required to communicate, exploit and work effectively across disciplinary and sectoral boundaries. Therefore, PROLUNG brings together top-scientists from the fields of both preclinical and clinical research fields, including ICU medicine and anesthesiology, pulmonology and physiology, biomedical science and technology, and health economic research, from both academic and non-academic institutions. Moreover, PROLUNG envisages that innovative training program will lead to collaborations beyond the network’s lifetime that will facilitate the further development and optimization of programs for training future cohorts of researchers. These future researchers will be trained in their roles as coordinators of preclinical animal studies, and international multicenter observational studies and randomized controlled clinical trials in the near future. Finally, the ESRs will be able to valorize and exploit knowledge and technologies to smoothen implementation of those preventive strategies that have been found (cost)-effective and safe.

A new project - a new grant application
Presently PROLUNG applies for an European grant within the Marie Sklodowska-Curie actions. 

Background
Mechanical ventilation has a strong potential to harm lungs and respiratory muscles: ventilator-induced lung injury (VILI) results, at least in part from the energy repeatedly transferred from the ICU ventilator to patient’s lungs; development of ventilator-induced diaphragm dysfunction (VIDD) is caused, at least in part by patient-ventilator asynchrony.
Two promising approaches to prevent VILI are to bypass the lungs for gas exchange, using hybrid or complete extracorporeal removal of CO2 (so-called extracorporeal CO2 removal, ECCO2R), and to decrease CO2 production by lowering metabolism through induced mild hypothermia. There are, however, several feasibility and safety issues that currently limit the widespread use of ECCO2R, including uncertainties regarding the amount of CO2 that can and should be removed with ECCO2R, gas compositions for ventilation when using hybrid ECCO2R, ventilator adjustments with hybrid ECCO2R, and anticlotting strategies. Furthermore, it is uncertain what body temperature to target for metabolism reduction. 
A promising strategy to improve patient-ventilator synchrony is the use of non-invasive sensors and software algorithms that adequately translate surface electromyogram (sEMG) readings of respiratory muscles into breath-triggers for ICU ventilators. It is uncertain, however, whether this approach is feasible and safe in all critically ill patient categories, and whether sEMG readings truly can be translated and integrated with presently used pneumatic readings into breath-triggers for ventilators. 

Feasibility and safety issues of ECCO2R and sEMG-based ventilation
Feasibility and safety issues that currently limit the widespread use of ECCO2R and temperature manipulations in an attempt to prevent VILI include: 
· Uncertainty on how much CO2 can and should be removed with the use of hybrid or complete ECCO2R 
· Uncertainty on what gas compositions for ventilation to use with hybrid ECCO2R 
· Uncertainty on how to adjust the ventilator with the use hybrid ECCO2R 
· Uncertainty on anticlotting strategies with ECCO2R 
· Uncertainty on safety and efficacy of body temperature manipulations to reduce CO2 production 
Feasibility and safety issues that currently limit use of sEMG readings in an attempt to reduce VIDD include: 
· Uncertainty on whether the presently available muscle sensors can capture sEMG readings of respiratory muscles in all critically ill patients categories
· Uncertainty regarding respiratory muscl
e selection for capturing sEMG
· Uncertainty on the translation of and integration of captured sEMG readings with presently used pneumatic readings into breath-triggers in ICU ventilators

The aims of this project
The abovementioned uncertainties need to be clarified before hybrid or complete ECCO2R, body temperature manipulations and sEMG-based ventilation can be compared with conventional mechanical ventilation strategies in randomized controlled clinical trials in ICU patients.

Scientific and technological objectives of PROLUNG:

1

Identifying the feasibility and safety of hybrid or complete ECCO2R, and the effects on VILI.

2

Identifying the feasibility and safety of closed-loop ventilation with hybrid ECCO2R, and the effects on VILI.

3

Identifying the feasibility and safety of temperature change to reduce CO2 production, and the effects on VILI.

4

Identifying the feasibility and safety of sEMG-based ventilation, and the effects on VIDD.


Participants
Nine university hospitals - including: Academisch Medisch Centrum, Amsterdam and VU Medical Center, The Netherlands (M. Schultz, J. Horn, N. Juffermans, C. Ottenheim), Universitätsklinikum Carl Gustav Carus – Technische Universität Dresden (M. Gama de Abreu), Fundació Parc Taulí, Barcelona, Spain (A. Artigas Raventos), Università degli Studi di Genova, Genova, Italy (P. Pelosi), Leuven University, Leuven, Belgium (G. Hermans), Universitätsklinikum Regensburg, Regensburg, Germany (T. Bein), Universität Zürich, Zürich, Switzerland (M. Maggiorini), Hôspital Sainte Musse, Toulon, France (J.M. Arnal), Queen’s University of Belfast, Belfast, UK (D. McAuley), and NUI-Galway, Galway, Ireland (J. Laffey) - and nine companies - including but not restricted to: Novalung, Germany (G. Matheis), Hamilton Medical, Switzerland (D. Novotni), Better Care, Spain (L. Blanche), and Inbiolab, The Netherlands (J. Vellinga) - in eight European countries join the consortium.

Discussion
The PROLUNG training network is opportune from a healthcare perspective, as it will provide a wealth of information and possibilities of hybrid or complete ECCO2R, temperature manipulations and sEMG-based ventilation in animals studies and pilot studies in human. PROLUNG comprises two tightly linked intersectoral components – research and complementary training – that will be implemented at local as well as network level and which will be united by individual personal career development plans carefully elaborated for each Early Stage Researcher (ESR) recruited. In particular, PROLUNG will harness complementary public and private sector expertise in research, training, market identification and knowledge exploitation to develop a lasting legacy of research training in ventilation research through cutting edge projects and extensive training in complementary areas in Europe.


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